Whelan, Ian T;
Burdis, Ross;
Shahreza, Somayeh;
Moeendarbary, Emad;
Hoey, David A;
Kelly, Daniel J;
(2023)
A microphysiological model of bone development and regeneration.
Biofabrication
, 15
(3)
, Article 034103. 10.1088/1758-5090/acd6be.
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Abstract
Endochondral ossification (EO) is an essential biological process than underpins how human bones develop, grow, and heal in the event of a fracture. So much is unknown about this process, thus clinical manifestations of dysregulated EO cannot be adequately treated. This can be partially attributed to the absence of predictive in vitro models of musculoskeletal tissue development and healing, which are integral to the development and preclinical evaluation of novel therapeutics. Microphysiological systems, or organ-on-chip devices, are advanced in vitro models designed for improved biological relevance compared to traditional in vitro culture models. Here we develop a microphysiological model of vascular invasion into developing/regenerating bone, thereby mimicking the process of EO. This is achieved by integrating endothelial cells and organoids mimicking different stages of endochondral bone development within a microfluidic chip. This microphysiological model is able to recreate key events in EO, such as the changing angiogenic profile of a maturing cartilage analogue, and vascular induced expression of the pluripotent transcription factors SOX2 and OCT4 in the cartilage analogue. This system represents an advanced in vitro platform to further EO research, and may also serve as a modular unit to monitor drug responses on such processes as part of a multi-organ system.
| Type: | Article |
|---|---|
| Title: | A microphysiological model of bone development and regeneration |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1088/1758-5090/acd6be |
| Publisher version: | https://doi.org/10.1088/1758-5090/acd6be |
| Language: | English |
| Additional information: | © The Author(s). Original content from this work may be used under the terms of the Creative Commons Attribution 4.0 license. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI. |
| Keywords: | development, microphysiological, model, bone, organ on chip |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10173130 |
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